The goal of this study is to elucidate the role of cell movement and contact behavior (including contact inhibition) in the invasive behavior of malignant B16 murine melanoma tumor cells. Two alternative hypotheses will be tested to explain tumor cell invasiveness: (1) that they have lost their susceptibility to contact inhibition of movement or (2) that they are able to avoid the effects of contact inhibition by moving on available extracellular substrata and avoiding inhibiting contacts with normal tissue cells. Variant sublines of B16, which exhibit quantitative differences in their ability to invade locally into tissues and to metastasize to the lungs, lymph nodes, mesentery, or other organs of syngeneic C57/BL6 mice, will be examined for their contact behavior and invasiveness in vitro. Tumor cell motility, contact behavior, and frequency of contact inhibition of movement will be assayed in monolayer cultures in which populations of B16 cells are confronted with populations of normal murine cells. A qualitative and quantitative analysis of cell movement and contact behavior will be carried out using time lapse cinemicrography of living cells and statistical analysis of the distribution of cells in fixed cultures. The invasive behavior of B16 cells will be studied in organ cultures of murine mesentery. The interactions of different variant sublines of B16 with the cells and extracellular matrix of the mesentery will be observed directly, using time lapse cinemicrography to record cell behavior. In addition, scanning and transmission electron microscopy will be used to monitor the process of invasion and to analyze the effects of invading cells on the extracellular matrix and normal cell population of the mesentery. The data on cell behavior and invasion will then be analyzed statistically and correlated with quantitative data on the invasive ability of the same subline of cells in vivo, in order to determine which aspects of cell social behavior in two and/or three dimensions are either positively or negatively correlated with invasiveness in vivo. (O)